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North American paragonimiasis: epidemiology and diagnostic strategies Expert Rev. Anti Infect. Ther. Early online, 1–8 (2015)

Peter U Fischer* and Gary J Weil Department of Internal Medicine, Infectious Diseases Division, Washington University School of Medicine, 660 S Euclid Avenue, St. Louis, MO 63110, USA *Author for correspondence [email protected]

Paragonimiasis is a zoonotic, food-borne trematode infection that affects around 23 million people in Asia, Africa and the Americas. North American paragonimiasis, caused by Paragonimus kellicotti, is a common infection of crustacean-feeding mammals in parts of the USA and Canada. Although infection rates in crayfish are very high in some areas, human infections are rare and depend on the consumption of raw or undercooked crayfish. Human infections can be easily prevented and treated, but proper diagnosis of paragonimiasis is a problem. Paragonimus lung flukes often cause serious disease symptoms before they produce eggs that may be detectable in sputum, bronchoalveolar lavage, stool or histological sections by microscopy or PCR. Antibodies against selected Paragonimus proteins are detectable as early as 2–3 weeks after infection. Therefore, antibody serology is the most promising diagnostic approach for paragonimiasis in North America and elsewhere. KEYWORDS: diagnosis . lung disease . Paragonimus infection . serology . zoonosis

Background

North American paragonimiasis (NAP) is caused by the food-borne trematode Paragonimus kellicotti. This lung fluke infection is rare in humans, but it is widely distributed in its animal reservoir and occurs in most parts of the United States and southern Canada, east of the Rocky Mountains [1,2]. Food-borne trematodes infect an estimated 56 million people worldwide, and more than a billion people live in areas with high infection risk. About 40% of these food-borne trematode infections are caused by members of the lung fluke genus Paragonimus, mostly in east Asia, but also in other parts of Asia, Africa and the Americas [3]. Because patients with paragonimiasis often present with chronic cough and hemoptysis, this infection is often confused with pulmonary tuberculosis or lung cancer in different regions of the world [4–6]. In some areas of the Philippines, a significant percentage of patients visiting pulmonary tuberculosis clinics are infected with Paragonimus, and integrated surveillance with tuberculosis has been suggested because both are co-endemic [6]. The diagnosis of human Paragonimus infection is difficult for several reasons. Firstly, immature lung flukes informahealthcare.com

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may cause severe clinical symptoms as they migrate through tissues, weeks or months before they shed eggs that can be detected in sputum and/or stool by microscopy. Secondly, parasitological detection of worm eggs by microscopy is often insensitive and requires specific experience. Molecular detection of parasite DNA appears more sensitive than microscopy, but this also depends on the presence of eggs in clinical specimens, and it requires specialized laboratory facilities. Specific molecular assays are not widely available, even in reference laboratories. Thirdly, it has been difficult to develop sensitive and specific serological tests for paragonimiasis, and there are no commercially available antibody test kits for paragonimiasis at this time. A number of recent reviews have focused on the pathology and clinical presentation of paragonimiasis in the USA and in other regions [2,7,8]. Therefore, the present review will focus on the epidemiology and diagnostic methods for NAP in comparison with Paragonimus infections in other parts of the world. Life cycle

Paragonimus larvae are transmitted via consumption of raw or undercooked crabs or

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ISSN 1478-7210

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the cercariae migrate to the heart muscle and transform into the encysted metacercariae (FIGURES 1 & 2). P. kellicotti metacercariae are about 500 mm in diameter and have a morphology characteristic for Paragonimus species with two cyst membranes, dark excretion material in the excretory bladder at the center 1 cm 1 cm and multiple intestine coils in the periphery. Figure 1. Second intermediate host for Paragonimus kellicotti. (A) A spothanded crayfish (Orconectes punctimanus) from the Huzzah River, a common species in the eastLung flukes are common parasites of ern part of the Ozark region in Missouri that is frequently infected with Paragonimus mammals that feed on crustaceans in kellicotti. (B) A dissected O. punctimanus with a P. kellicotti metacercaria in the heart (a many parts of the world. However, small white spot indicated by an arrow). human infections require consumption of raw or undercooked crustaceans, and crayfish that contain infectious metacercariae. Paratenic mamma- this depends on local dietary preferences. Paragonimus infeclian hosts that carry infectious parasites, but not mature parasites, tion can be prevented by public health education emphasizing appear to play a minor role in the transmission cycle in parts of the dangers of consuming raw freshwater crustaceans, but it Asia [9]. Most of what is known about the development and dis- can sometimes be difficult to change behavior. When the tribution of P. kellicotti has been summarized by Donald Ameel infection is diagnosed, it can be easily treated with praziquanin 1934, and up-to-date data using modern morphologic, immu- tel (three doses of 25 mg/kg body weight/day for 3 days) or nologic, molecular biological or genomic methods are scarce for triclabendazole as the secondary choice (10 mg/kg body this species [10]. P. kellicotti larvae excyst in the intestine of the weight for 3 days) [16–18]. Unfortunately, diagnosis of human definitive host, penetrate the intestinal wall within hours, and paragonimiasis is often difficult. For this reason, there are no migrate through the peritoneal cavity toward the pleural space. reliable estimates of prevalence or economic impact for paraHepatic paragonimiasis lesions in humans that can be confused gonimiasis in most endemic regions. with liver cancer have been described from Asian Paragonimus species [11]. However, majority of the young lung flukes pene- Epidemiology trate the diaphragm and enter the pleural cavity within 1–3 weeks Transmission after infection. The larvae stimulate an inflammatory response About 30 species of the genus Paragonimus have been with pleural effusion, and patients sometimes experience sharp described and half of these are known to infect humans. Lung pleural pain with cough and fever. Later, the young flukes invade flukes are widely distributed in mammalian hosts in most parts the lung where they induce formation of a fibrous cyst. Approxi- of Asia, Africa and the Americas, but the frequency of transmately 6 weeks after infection, the hermaphroditic flukes start to mission to humans depends on dietary practices, especially on release eggs that may be detected in the lung tissue, sputum, whether people consume raw or undercooked freshwater crusstool and the pleural cavity. Little is known about the reproduc- taceans [9]. In China and some regions of southeast Asia, certive life span of P. kellicotti, but other Paragonimus species can tain traditional dishes include raw or undercooked crabs or produce eggs for more than two decades [12]. Eggs can be crayfish, and this promotes the transmission of Paragonimus to coughed into sputum or swallowed and excreted with stool. humans [19]. More than 90% of the human infections are estiAppropriate temperature and water contact are necessary for the mated to occur in these regions [3]. Similarly, in South P. kellicotti eggs to fully develop. Therefore, it may take up to America, some indigenous tribes have a high risk for paragoni6 months until the ciliated miracidia larvae hatch. These free- miasis because of their local food preparation habits [20]. In living larvae penetrate aquatic snails within hours. The slender Africa, it is sometimes common among children to partially walker snail, Pomatiopsis lapidaria, was reported in 1932 as the roast crabs on a stick or to chew on moving crab legs as part first intermediate host for P. kellicotti [10], but no recent data on of a game [21]. While ingestion of raw crustaceans is not comits snail hosts are available. Although the first intermediate host mon in North America, people sometimes ingest raw crayfish for many trematode species is relatively species specific, some on camping or canoeing trips. In some cases, this is in Paragonimus species have more than one snail host. For example, response to encouragement from friends; many patients report P. skrjabini utilizes more than 25 species of snails across three having been intoxicated when they ingested raw crayfish. In families as its first intermediate host [13]. Asexual reproduction of these cases, alcohol may have reduced the inhibitions regarding P. kellicotti occurs exclusively in the snail host, where miracidiae dietary practices [1,22]. Therefore, NAP infections occur in the develop into sporocysts that produce two generations of rediae. late spring, summer and early fall. The interval between ingesThe rediae release many cercariae, which are small larvae with a tion of crayfish and the onset of symptoms can be weeks or short tail that swim in water [14]. Cercariae attach to crayfish by months, and many months may pass before patients are propsecretion of a mucoid coat [15]. After penetration of the cuticle, erly diagnosed and treated.

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Human infections represent a dead end for the transmission cycle of P. kellicotti, but the infection is maintained in a sylvatic cycle with a variety of mammals that feed on crayfish (mink, otter, skunk, fox, bobcat, coyote, muskrat, possum and raccoon) serving as definitive hosts [10,23–26]. Infection rates in natural definitive hosts vary geographically, seasonally and by host species. For instance, in some areas, crayfish are the dominant prey for mink and otter, especially during summer, and the infection rates can be high. In contrast, the infection rates tend to be low in coyotes, which rarely feed on crayfish [25]. Domestic or feral cats and dogs are also permissive hosts and sometimes naturally infected, but they are not likely to contribute to the transmission cycle [27–29]. In the laboratory, rats, Syrian hamsters, Mongolian gerbils and Rhesus monkeys support the development of P. kellicotti, but infections sometimes cause the death of the host [14,30,31]. To summarize this section, P. kellicotti shows little host specificity regarding definitive hosts, and many mammals including humans are permissive hosts. Distribution

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Figure 2. Infectious metacercariae, adult fluke and eggs of Paragonimus kellicotti. (A) Four metacercariae of Paragonimus kellicotti in the heart of a crayfish from Missouri. (B) An immature P. kellicotti fluke (28 days pi) isolated from the pleural cavity of an experimentally infected Mongolian gerbil. (C) P. kellicotti egg in the sputum of a patient from Missouri. (D) P. kellicotti eggs (arrows) in sputum sediment from a patient from Missouri. (E) Many P. kellicotti eggs (arrow) in the lung cyst tissue of an experimentally infected gerbil (42 days pi) (H & E stain). (F) A magnified P. kellicotti egg from the same tissue section as in (E) showing the thick egg shell (arrow). (C–F) Show P. kellicotti eggs as they are sometimes, but not always, observed in clinical North American paragonimiasis cases. Op: Operculum; Os: Oral sucker; vs: Ventral sucker.

The distribution of NAP was first outlined by Ameel in 1934 with records of infected crayfish or definitive hosts from southern Ontario, North and South Dakota, Minnesota, Wisconsin, Michigan, Iowa, Illinois, Indiana, Ohio, Pennsylvania, Missouri, West Virginia, Virginia, Louisiana and Mississippi [10]. In addition, P. kellicotti was also reported to be present in Kentucky, Georgia and Oklahoma [23,32,33]. In most cases, these records date from the middle of the last century and the current distribution is unknown. There is no convincing evidence for the distribution of P. kellicotti outside North America, and single case reports of P. kellicotti in Israel or South Africa are most likely due to species misidentification [34,35]. The complex life cycle of P. kellicotti requires not only the simultaneous presence of appropriate first, second and definitive hosts, but also suitable environmental conditions that include periodic flooding to submerge animal feces to enable hatching of miracidiae and infection of snails. Therefore, the distribution of crayfish containing infectious metacercariae is often focal. For example, we have observed a high infection rate of crayfish in a Missouri creek, but found no metacercariae in the crayfish from a nearby pond. On the other hand, infected snails can produce cercariae for many months without the need to acquire a new infection, and metacercariae in crayfish appear to remain infectious for the life of the crayfish plus a few days [26]. informahealthcare.com

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Prevalence

As mentioned earlier, prevalence of human paragonimiasis is dependent on the abundance of infection in animals and the prevalence of infectious metacercariae in crustacean hosts. More importantly, infection risk for humans depends on ingestion of raw or undercooked crabs or crayfish. Crayfish are commonly eaten in parts of the USA, especially in Louisiana. However, most of these crayfish are raised in ponds [36] and not infected with P. kellicotti. Also, crayfish are cooked before they are eaten in Louisiana. The consumption of raw crayfish in the USA can also lead to other health risks such as bacterial gastroenteritis [37]. Little data exist on the prevalence of P. kellicotti metacercariae in river crayfish. Seasonal variation of P. kellicotti metacercariae infection rates in crayfish was observed in central Ohio in the 1970s, with lower infection rates in spring and early summer and higher rates of about 90% in late summer and autumn [26]. A more recent study from southern Missouri showed that 60% of larger (>3 cm) crayfish specimens of the common species Orconectes punctimanus, Orconectes luteus and Orconectes virilis collected between May and September contained metacercariae [30]. Assuming an average number of three metacercariae per crayfish and a development rate of 50% after ingestion, every second crayfish consumed raw or undercooked doi: 10.1586/14787210.2015.1031745

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from these areas is likely to result in a NAP infection. Accordingly, NAP appears to be an emerging infection in the US. Only six human cases of NAP were reported from Colorado, Iowa, Michigan, Missouri and Oklahoma between 1965 and 2007. Between 2008 and 2012, 14 additional cases had been published from Missouri alone [1,22]. It is not known whether this was entirely due to an increased incidence or partially due to an increased awareness of the problem among physicians. A modest health education campaign was conducted in 2010– 2011. Posters warning of the danger of eating raw crayfish were distributed to camp grounds and canoe rental companies. The Missouri health department sent a health advisory to physicians in the state, and press releases, television interviews and newspaper articles highlighted the problem for the public [1]. It is likely that this campaign helped to reduce the incidence of NAP in Missouri; only two new cases were observed in 2013–2014. It is also possible that reduced rain/flooding and lower crayfish densities may have played a role, but we have no data to support this hypothesis. Diagnostic strategies Classical parasitology

Laboratory diagnosis of NAP by microscopy is difficult because many infected individuals do not have eggs detectable in stool, sputum, bronchoalveolar lavage fluid, pleural effusions or lung biopsies. P. kellicotti requires 6–8 weeks to start producing eggs in the mammalian host. Previous case reports have shown that months or years may pass between the onset of the illness and parasitological diagnosis [2,8]. Diagnosis was often delayed for many months after the onset of symptoms, and patients repeatedly failed therapeutic trials of antibiotics and/or steroids prior to proper diagnosis and treatment [1]. In patent Paragonimus infections, eggs can be detected by microscopy in both stool and sputum, but the detection rates in sputum are usually higher [38]. Several different methods can be used for detecting eggs in stool, including direct smear, Kato Katz smear, formalin-ether sedimentation and zinc sulfate flotation. A study from the Lao Republic reported that Paragonimus eggs can be detected in sputum by direct smear, formalin-ether concentration and by Ziehl-Neelsen staining used for the detection of Mycobacteria [39]. P. kellicotti eggs have been detected in the sputum by direct smear in a few cases [40]. P. kellicotti eggs are recognizable in the histological sections of lung by their characteristic thick brownish egg shell in sections stained with hematoxylin and eosin (FIGURE 2F). Unfortunately, few high-quality images of P. kellicotti from human cases have been published, and the morphology of the parasites and ova can vary according to the sample type, fixation method and staining technique. Infectious metacercariae, an immature fluke and eggs in different clinical samples are shown in FIGURE 2A–2F. Clinical diagnosis

The clinical signs of human NAP range from asymptomatic eosinophilia to severe lung disease with pleural effusions, pneumothorax and hemoptysis [1,2,7,22]. The most common sign of doi: 10.1586/14787210.2015.1031745

pulmonary paragonimiasis is a chronic cough with brownish, blood-streaked sputum. Most cases of human NAP have presented with moderate to severe lung disease, and there is no evidence for asymptomatic infections which have been described for other Paragonimus species. Some studies from Asia have described different disease presentations according to the infecting parasite species [41]. However, pleural and pulmonary features of NAP are generally similar to those reported from Asia [42]. Since only relatively few human NAP cases have been reported, there is little reason to assume that P. kellicotti infection causes fundamentally different pathology compared to other Paragonimus species. Asian Paragonimus species sometimes migrate to ectopic locations (subcutaneous tissue, omentum) in 5% of the clinical cases, and about 1% of all clinical paragonimiasis cases present with cerebral disease [43–46]. An example for an odd ectopic location is an immature P. westermani fluke that was found in a cyst at the tip of the little finger in a woman with severe pulmonary paragonimiasis, from Korea [47]. Sometimes pulmonary or cerebral cases lead to fatal outcomes [3,48,49]. Reports of NAP have also included cases with pericarditis, pericardial tamponade, cerebral involvement and subcutaneous nodules [1,8]. DNA-based diagnostics

Many DNA-based diagnostic assays have been reported for NAP and other Paragonimus species. These assays include conventional PCR [30,50–53], quantitative PCR [54] and loopmediated amplification [55]. Unfortunately, no study has compared the relative sensitivity of different DNA-based diagnostic tests for paragonimiasis with large numbers of human sputum or stool samples. As with microscopy, the sensitivity of DNA detection depends on the presence of eggs in the clinical sample, and therefore, pre-patent infections will not be detected by PCR. Another use of DNA-based assays is in the identification and differentiation of Paragonimus species in intermediate and definitive hosts [56,57]. However, the total amount of DNA sequence information for Paragonimus available until recently was limited to a couple of ribosomal and nuclear markers, and no complete genome data was available to facilitate the development of novel molecular markers needed for thorough molecular epidemiology studies [9]. Next-generation DNA sequencing platforms have recently led to genome and transcriptome sequencing of P. kellicotti, P. westermani and Paragonimus miyazakii [58], and this information will be important for future research. Serological diagnostics

There is currently no assay available for detection of P. kellicotti antigen in human samples. Antigen assays based on monoclonal antibodies have been described for diagnosis of paragonimiasis caused by other species [59–61]. Unfortunately, these assays have not been independently evaluated for sensitivity and specificity with large panels of patient sera, sera from patients with other food-borne trematode infections or other helminth infections. Since part of the pathology in paragonimiasis is caused by the small, migrating, immature lung flukes that do not shed eggs, Expert Rev. Anti Infect. Ther.

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North American paragonimiasis

it is unlikely that immature stages release sufficient antigen for detection in human sera. In contrast to parasite antigens, antibodies to P. kellicotti antigens can be detected in humans and in experimental animals as early as 2 weeks after infection, long before eggs are detectible in clinical samples and prior to the onset of clinical signs of infection [30,62]. Crude worm extracts or fractionated, native antigens from several Paragonimus species have been used for serological diagnosis with varying degrees of success. Generally, cross-reactivity of antibodies across different trematode species has been a problem for serodiagnosis [63,64]. However, this is less of a problem for serodiagnosis of NAP because trematode infections in humans are generally very rare in North America. Several platforms have been used for Paragonimus antibody detection, including intradermal skin tests [65], indirect hemagglutination assays [66], ELISA [67], western blot [62,68] and a rapid immunochromatographic strip test [69]. Usually antibody detection assays do not discriminate between Paragonimus species, but use of antigen from homologous species may improve the sensitivity [62]. Antibody assays using recombinant Paragonimus antigen(s) might be more sensitive and specific than the assays based on native antigens. For example, a recombinant P. westermani egg yolk antigen with diagnostic potential was described several years ago, but it was evaluated with relatively few sera from patients with eggs in sputum who were identified during epidemiological surveys [70–72]. Although the specificity of the egg antigen was estimated to be close to 100%, its sensitivity was only 90% and pre-patent cases were not included in the study [72]. It is doubtful whether all paragonimiasis cases can be detected by antibody tests using an egg antigen because patients sometimes present with symptoms long before the worms begin to produce eggs. Excretory/secretory antigens of immature lung flukes that migrate in tissues might be better candidates for detecting early infections. A recent proteomics study identified an immunodominant, excreted cysteine protease in P. westermani [73]. However, an ELISA based on a peptide sequence from the parasite cysteine protease lacked specificity for paragonimiasis [74]. On the other hand, some recombinant cathepsin F–type cysteine proteases have been reported to be promising candidate antigens for serodiagnosis [75]. Extensive proteomic analysis of Paragonimus antigens has been hampered so far by the scarcity of genome/transcriptome information for Paragonimus. This information is crucial for proper peptide identification in proteomic studies. With the exception of some mitochondrial and nuclear DNA markers, a few selected cDNA sequences and about 1500 expressed sequence tags of P. westermani, no genetic information for Paragonimus existed until recently [76]. Transcriptome sequencing of adult stage P. kellicotti identified 78,000 unique transcripts, and enabled not only the proteomic identification of about 2500 proteins but also the detection of immunodominant P. kellicotti proteins that could be targets for antibody detection assays [77]. The use of patient sera from areas where other helminth infections are highly prevalent, for the identification of informahealthcare.com

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immunodominant Paragonimus antigens can be problematic. Co-existing helminth antibodies that may recognize conserved Paragonimus antigens may lead to the detection of cross-reactive antigens by immunoscreening of Paragonimus cDNA expression libraries or by immunoprecipitation of Paragonimus antigens. Therefore, the use of well-defined patient sera from areas that are not co-endemic for other helminth species (e.g., samples from NAP patients) may be especially useful for this purpose, because most people living in North America have not been infected by other trematode parasites. The potential public health value of improved diagnostic tests for paragonimiasis

Parasites of the genus Paragonimus appear to be taxonomically diverse, but they contain many cross-reactive antigens [63]. All the species tested so far have responded similarly to treatment, and species identification is not necessary to make treatment decisions. A species-specific diagnostic test would have less value as a global health tool than a test that detects antibodies in patients infected with any Paragonimus species with a high sensitivity. NAP can be used as a field model for the development of paragonimiasis serology. While antibody serology cannot always distinguish between current and past infections, treatment with praziquantel is safe and overtreatment is not a problem. Praziquantel is used for mass drug administration in children and adults for the control and local elimination of schistosomiasis [78], and this may be a useful option for areas with high rates of paragonimiasis. Expert commentary

NAP is a rare zoonotic helminth infection that can be easily prevented and treated in humans. However, the parasite can cause severe disease if diagnosis and treatment are delayed. Approximately 16 cases of NAP have been reported from Missouri since 2008, and the incidence of the disease seems to have decreased over the past 2 years. Despite increased awareness among physicians and occasional efforts to reinforce the message about the danger of eating raw crayfish, it is likely that sporadic new cases will continue to occur. Better diagnostic testing will lead to earlier diagnosis and treatment and better outcomes for the patients and their families. Although it appears that there would be little financial incentive for the development of improved diagnostic tests for NAP, a sensitive and genus-specific test could be commercially viable both for diagnosis of individual patients and as a public health tool in many countries in Asia and Latin America where paragonimiasis infections are common. Improved diagnostic tests for paragonimiasis may also be useful for veterinary medicine. Five-year view

The development of standardized serological diagnostics will improve the diagnosis of NAP and other Paragonimus infections. Genome sequences of P. kellicotti and two other Paragonimus species are available [79] and more are on the way. This information will facilitate and speed up the development of doi: 10.1586/14787210.2015.1031745

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standardized serological tests for paragonimiasis. Improved diagnostic tests for paragonimiasis will not only help to better manage human infections, but also reduce misdiagnosis, since paragonimiasis is often confused with tuberculosis and lung cancer. Thus, patients in areas with paragonimiasis who are suspected of having tuberculosis or lung cancer should be tested for paragonimiasis. There are many reports of putative tuberculosis cases that are diagnosed with paragonimiasis after they fail to improve on anti-tuberculosis medications [47]. On an individual level, accurate identification of human Paragonimus infections will help to reduce suffering and costs associated with mistreatment and progression of disease due to delayed diagnosis. As it is a zoonosis, paragonimiasis is not likely to be eliminated anytime soon. However, our local experience with NAP points to measures that could greatly reduce the public health impact of paragonimiasis in other parts of the world. These include public health education to change dietary practices (to avoid ingestion of metacercariae present in

uncooked freshwater crabs and crayfish) and earlier diagnosis and treatment facilitated by improved diagnostic tests. Among the so-called ‘neglected tropical diseases’, paragonimiasis represents an attractive target for focused effort because of the following: its public health importance in Asia, ingestion of raw crustaceans is necessary for transmission and it is easily treated with oral praziquantel. Widespread availability of a sensitive antibody test that detects antibodies to the major Paragonimus species could lead to rapid progress in the control of paragonimiasis. Financial & competing interests disclosure

This work has been supported by a grant of the Barnes Jewish Hospital Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Key issues .

While the infection risk of paragonimiasis for humans can be reduced or eliminated by avoiding exposure to metacercariae, infection rates in crustaceans in most areas of the world do not depend on humans.

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In addition to the clinical and parasitological diagnostic approaches, immunodiagnosis with crude Paragonimus antigens as performed at the US Centers for Disease Control or in our laboratory can be useful for confirming diagnoses.

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Further genomic and proteomic information will facilitate progress in the development of standardized serodiagnostic assays using recombinant Paragonimus antigens.

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Improved diagnosis of human paragonimiasis will also improve differential diagnosis of other lung diseases, since clinical features of paragonimiasis (cough, fever, weight loss, chest pain, hemoptysis) overlap with those in patients with tuberculosis and lung cancer.

References

4.

Papers of special note have been highlighted as: . of interest .. of considerable interest 1.

Lane MA, Marcos LA, Onen NF, et al. Paragonimus kellicotti flukes in Missouri, USA. Emerg Infect Dis 2012;18:1263-7

.

Comprehensive clinical description of six North American paragonimiasis (NAP) cases.

2.

.

Procop GW. North American paragonimiasis (Caused by Paragonimus kellicotti) in the context of global paragonimiasis. Clin Microbiol Rev 2009;22:415-46 Review on NAP and global paragonimiasis.

3.

Furst T, Keiser J, Utzinger J. Global burden of human food-borne trematodiasis: a systematic review and meta-analysis. Lancet Infect Dis 2012;12:210-21

..

An excellent review of the global burden of food-borne trematodes.

doi: 10.1586/14787210.2015.1031745

5.

6.

7.

8.

Lee S, Yu Y, An J, et al. A case of delayed diagnosis of pulmonary paragonimiasis due to Improvement after anti-tuberculosis therapy. Tuberc Respir Dis (Seoul) 2014;77:178-83 Hwang KE, Song HY, Jung JW, et al. Pleural fluid characteristics of pleuropulmonary paragonimiasis masquerading as pleural tuberculosis. Korean J Intern Med 2015;30: 56-61 Belizario V Jr, Totanes FI, Asuncion CA, et al. Integrated surveillance of pulmonary tuberculosis and paragonimiasis in Zamboanga del Norte, the Philippines. Pathog Glob Health 2014;108:95-102 Diaz JH. Paragonimiasis acquired in the United States: native and nonnative species. Clin Microbiol Rev 2013;26: 493-504 Lane MA, Barsanti MC, Santos CA, et al. Human paragonimiasis in North America following ingestion of raw crayfish. Clin Infect Dis 2009;49:e55-61

9.

Blair D. Paragonimiasis. Adv Exp Med Biol 2014;766:115-52

.

Review focusing on the biology of Paragonimus parasites.

10.

Ameel DJ. Paragonimus, its life history and distribution in North America and its taxonomy (Trematoda: troglotermatidae). Am J Hyg 1934;19:279-317

11.

Lu Q, Ling WW, Ma L, et al. Contrast-enhanced ultrasonographic findings of hepatic paragonimiasis. World J Gastroenterol 2013;19:2087-91

12.

Ikehara M, Komase Y, Morita A, et al. Paragonimiasis in a person whose symptoms were shown 22 years after emigrating to Japan from Laos. J Infect Chemother 2010;16:49-52

13.

Attwood SW. Studies on the parasitology, phylogeography and the evolution of host-parasite interactions for the snail intermediate hosts of medically important trematode genera in Southeast Asia. Adv Parasitol 2010;73:405-40

Expert Rev. Anti Infect. Ther.

North American paragonimiasis

14.

Sogandares-Bernal F, Seed JR. American paragonimiasis. Curr Top Comp Pathobiol 1973;2:1-56

15.

Gyoten J. Infection by Paragonimus miyazakii cercariae of their crab hosts, Geothelphusa dehaani, by percutaneous penetration. J Parasitol 2000;86:1342-5

Expert Review of Anti-infective Therapy Downloaded from informahealthcare.com by Nanyang Technological University on 04/25/15 For personal use only.

16.

Johnson RJ, Jong EC, Dunning SB, et al. Paragonimiasis: diagnosis and the use of praziquantel in treatment. Rev Infect Dis 1985;7:200-6

17.

Keiser J, Engels D, Buscher G, et al. Triclabendazole for the treatment of fascioliasis and paragonimiasis. Expert Opin Investig Drugs 2005;14:1513-26

18.

Nawa Y, Thaenkham U, Ngoc Doanh P, et al. Paragonimus westermani and Paragonimus species. In: Motarjemi Y, Moy G, Todd E, editors. Encyclopedia of food safety. Elsevier; 2014. p. 179-88

19.

20.

21.

22.

Sripa B, Kaewkes S, Intapan PM, et al. Food-borne trematodiases in Southeast Asia epidemiology, pathology, clinical manifestation and control. Adv Parasitol 2010;72:305-50 Calvopina M, Romero D, Castaneda B, et al. Current status of Paragonimus and paragonimiasis in Ecuador. Mem Inst Oswaldo Cruz 2014;109:849-55 Sachs R, Cumberlidge N. Distribution of metacercariae in freshwater crabs in relation to Paragonimus infection of children in Liberia, West Africa. Ann Trop Med Parasitol 1990;84:277-80 Centers for Disease Control Prevention. Human paragonimiasis after eating raw or undercooked crayfish – Missouri, July 2006-September 2010. MMWR Morb Mortal Wkly Rep 2010;59:1573-6

..

Epidemiological report on the human NAP cases in Missouri.

23.

Cole RA, Shoop WL. Helminths of the raccoon (Procyon lotor) in western Kentucky. J Parasitol 1987;73:762-8

24.

Hiestand SJ, Nielsen CK, Jimenez FA. Epizootic and zoonotic helminths of the bobcat (Lynx rufus) in Illinois and a comparison of its helminth component communities across the American Midwest. Parasite 2014;21:4

25.

Ramsden RO, Presidente PJ. Paragonimus kellicotti infection in wild carnivores in southwestern Ontario: I. Prevalence and gross pathologic features. J Wildl Dis 1975;11:136-41

26.

Stromberg PC, Toussant MJ, Dubey JP. Population biology of Paragonimus kellicotti

informahealthcare.com

metacercariae in central Ohio. Parasitology 1978;77:13-18 27.

Bech-Nielsen S, Fulton RW, Cox HU, et al. Feline respiratory tract disease in Louisiana. Am J Vet Res 1980;41:1293-8

28.

Kirkpatrick CE, Shelly EA. Paragonimiasis in a dog: treatment with praziquantel. J Am Vet Med Assoc 1985;187:75-6

29.

Pechman RD Jr. Pulmonary paragonimiasis in dogs and cats: a review. J Small Anim Pract 1980;21:87-95

30.

.

Fischer PU, Curtis KC, Marcos LA, et al. Molecular characterization of the North American lung fluke Paragonimus kellicotti in Missouri and its development in Mongolian gerbils. Am J Trop Med Hyg 2011;84:1005-11 Most recent infection rates of crayfish with Paragonimus kellicotti in Missouri.

Review

41.

Kanpittaya J, Sawanyawisuth K, Vannavong A, et al. Different chest radiographic findings of pulmonary paragonimiasis in two endemic countries. Am J Trop Med Hyg 2010;83:924-6

42.

Henry TS, Lane MA, Weil GJ, et al. Chest CT features of North American paragonimiasis. AJR Am J Roentgenol 2012;198:1076-83

43.

Chai JY. Paragonimiasis. Handb Clin Neurol 2013;114:283-96

44.

Chen J, Chen Z, Lin J, et al. Cerebral paragonimiasis: a retrospective analysis of 89 cases. Clin Neurol Neurosurg 2013;115: 546-51

.

Comprehensive report on a large number of cerebral paragonimiasis cases from China.

45.

Xia Y, Ju Y, Chen J, et al. Cerebral paragonimiasis: a retrospective analysis of 27 cases. J Neurosurg Pediatr 2015;15(1): 101-6

31.

Weina PJ, Burns WC. Mortality in Syrian hamsters infected with Paragonimus kellicotti. J Parasitol 1992;78:378-80

32.

McKeever S. Observations on Paragonimus kellicotti Ward from Georgia. J Parasitol 1958;44:324-7

46.

Xia Y, Ju Y, Chen J, et al. Hemorrhagic stroke and cerebral paragonimiasis. Stroke 2014;45:3420-2

33.

Castilla EA, Jessen R, Sheck DN, et al. Cavitary mass lesion and recurrent pneumothoraces due to Paragonimus kellicotti infection: north American paragonimiasis. Am J Surg Pathol 2003;27: 1157-60

47.

Sim YS, Lee JH, Hong SC, et al. Paragonimus westermani found in the tip of a little finger. Intern Med 2010;49:1645-8

48.

Blair D, Xu ZB, Agatsuma T. Paragonimiasis and the genus Paragonimus. Adv Parasitol 1999;42:113-222

Harrus S, Nyska A, Colorni A, et al. Sudden death due to Paragonimus kellicotti infection in a dog. Vet Parasitol 1997;71: 59-63

49.

Miyazaki I. Cerebral paragonimiasis. Contemp Neurol Ser 1975;12:109-32

50.

Intapan PM, Wongkham C, Imtawil KJ, et al. Detection of Paragonimus heterotremus eggs in experimentally infected cats by a polymerase chain reaction-based method. J Parasitol 2005;91:195-8

51.

Sugiyama H, Morishima Y, Kameoka Y, et al. Polymerase chain reaction (PCR)based molecular discrimination between Paragonimus westermani and P. miyazakii at the metacercarial stage. Mol Cell Probes 2002;16:231-6

52.

Sugiyama H, Morishima Y, Rangsiruji A, et al. Application of multiplex PCR for species discrimination using individual metacercariae of Paragonimus occurring in Thailand. Southeast Asian J Trop Med Public Health 2006;37(Suppl 3):48-52

53.

Vargas-Arzola J, Segura-Salvador A, Reyes-Velasco L, et al. Detection of Paragonimus mexicanus (Trematoda) metacercariae in crabs from Oaxaca, Mexico. Acta Trop 2014;137:95-8

54.

Tantrawatpan C, Intapan PM, Thanchomnang T, et al. Application of a real-time fluorescence resonance energy

34.

35.

McCallum SM. Ova of the lung fluke Paragonimus kellicotti in fluid from a cyst. Acta Cytol 1975;19:279-80

36.

Pflieger WL. The crayfish of Missouri. Missouri Department of Conservation; Jefferson City: 1996

37.

Kay MK, Cartwright EJ, Maceachern D, et al. Vibrio mimicus infection associated with crayfish consumption, Spokane, Washington, 2010. J Food Prot 2012;75: 762-4

38.

Johansen MV, Sithithaworn P, Bergquist R, et al. Towards improved diagnosis of zoonotic trematode infections in Southeast Asia. Adv Parasitol 2010;73:171-95

39.

Slesak G, Inthalad S, Basy P, et al. Ziehl-Neelsen staining technique can diagnose paragonimiasis. PLoS Negl Trop Dis 2011;5:e1048

40.

Mariano EG, Borja SR, Vruno MJ. A human infection with Paragonimus kellicotti (lung fluke) in the United States. Am J Clin Pathol 1986;86:685-7

doi: 10.1586/14787210.2015.1031745

Review

Fischer & Weil

transfer polymerase chain reaction assay with melting curve analysis for the detection of Paragonimus heterotremus eggs in the feces of experimentally infected cats. J Vet Diagn Invest 2013;25:620-6

Expert Review of Anti-infective Therapy Downloaded from informahealthcare.com by Nanyang Technological University on 04/25/15 For personal use only.

55.

56.

57.

58.

59.

60.

61.

62.

71.

Kim TY, Joo IJ, Kang SY, et al. Recombinant Paragonimus westermani yolk ferritin is a useful serodiagnostic antigen. J Infect Dis 2002;185:1373-5

72.

Lee JS, Lee J, Kim SH, et al. Molecular cloning and characterization of a major egg antigen in Paragonimus westermani and its use in ELISA for the immunodiagnosis of paragonimiasis. Parasitol Res 2007;100: 677-81

73.

Lee EG, Na BK, Bae YA, et al. Identification of immunodominant excretory-secretory cysteine proteases of adult Paragonimus westermani by proteome analysis. Proteomics 2006;6:1290-300

74.

Intapan PM, Sanpool O, Janwan P, et al. Evaluation of IgG4 subclass antibody detection by peptide-based ELISA for the diagnosis of human paragonimiasis heterotrema. Korean J Parasitol 2013;51: 763-6

75.

Doanh PN, Dung do T, Thach DT, et al. Human paragonimiasis in Viet Nam: epidemiological survey and identification of the responsible species by DNA sequencing of eggs in patients’ sputum. Parasitol Int 2011;60:534-7

Ahn CS, Na BK, Chung DL, et al. Expression characteristics and specific antibody reactivity of diverse cathepsin F members of Paragonimus westermani. Parasitol Int 2015;64:37-42

76.

Slemenda SB, Maddison SE, Jong EC, et al. Diagnosis of paragonimiasis by immunoblot. Am J Trop Med Hyg 1988;39:469-71

Kim TS, de Guzman JV, Kong HH, et al. Comparison of gene representation between diploid and triploid Paragonimus westermani by expressed sequence tag analyses. J Parasitol 2006;92:803-16

77.

McNulty SN, Fischer PU, Townsend RR, et al. Systems biology studies of adult Paragonimus lung flukes facilitate the identification of immunodominant parasite antigens. PLoS Negl Trop Dis 2014;8: e3242

.

A novel approach to identify immunodominant P. kellicotti antigens.

78.

Colley DG. Morbidity control of schistosomiasis by mass drug administration: how can we do it best and what will it take to move on to elimination? Trop Med Health 2014;42:25-32

79.

Available from: www.trematode.net/ TN_frontpage.cgi

Paragonimus kellicotti adult worm antigen. Am J Trop Med Hyg 2013;88:1035-40 .

First use of crude P. kellicotti antigen for human NAP serology.

63.

Kong Y, Ito A, Yang HJ, et al. Immunoglobulin G (IgG) subclass and IgE responses in human paragonimiases caused by three different species. Clin Diagn Lab Immunol 1998;5:474-8

64.

Narain K, Devi KR, Mahanta J. Development of enzyme-linked immunosorbent assay for serodiagnosis of human paragonimiasis. Indian J Med Res 2005;121:739-46

65.

Tantrawatpan C, Intapan PM, Janwan P, et al. Molecular identification of Paragonimus species by DNA pyrosequencing technology. Parasitol Int 2013;62:341-5

Sawada T, Takei K, Sato S, et al. Studies on the immunodiagnosis of paragonimiasis. 3. Intradermal skin tests with fractionated antigens. J Infect Dis 1968;118:235-9

66.

Martin J, Rosa BA, Ozersky P, et al. Helminth.net: expansions to Nematode.net and an introduction to Trematode.net. Nucleic Acids Res 2015;43(Database issue): D698-706

Knobloch J, Paz G, Feldmeier H, et al. Serum antibody levels in human paragonimiasis before and after therapy with praziquantel. Trans R Soc Trop Med Hyg 1984;78:835-6

67.

Maleewong W, Intapan PM, Priammuenwai M, et al. Monoclonal antibodies to Paragonimus heterotremus and their potential for diagnosis of paragonimiasis. Am J Trop Med Hyg 1997;56:413-17

68.

Chen MX, Ai L, Zhang RL, et al. Sensitive and rapid detection of Paragonimus westermani infection in humans and animals by loop-mediated isothermal amplification (LAMP). Parasitol Res 2011;108:1193-8 Biswal DK, Chatterjee A, Bhattacharya A, et al. The mitochondrial genome of Paragonimus westermani (Kerbert, 1878), the Indian isolate of the lung fluke representative of the family Paragonimidae (Trematoda). PeerJ 2014;2:e484

Maleewong W, Intapan PM, Wongkham C, et al. A dot-ELISA test using monoclonal antibody-purified antigens for the diagnosis of paragonimiasis caused by Paragonimus heterotremus. Southeast Asian J Trop Med Public Health 1997;28:621-3 Zhang Z, Zhang Y, Shi Z, et al. Diagnosis of active Paragonimus westermani infections with a monoclonal antibody-based antigen detection assay. Am J Trop Med Hyg 1993;49:329-34 Fischer PU, Curtis KC, Folk SM, et al. Serological diagnosis of North American paragonimiasis by western blot using

doi: 10.1586/14787210.2015.1031745

69.

.

70.

Wang Y, Wang L, Zhang J, et al. Preparation of colloidal gold immunochromatographic strip for detection of Paragonimiasis skrjabini. PLoS One 2014;9:e92034 Development of a rapid antibody test using excretory/secretory Paragonimus antigen. Kim TY, Joo IJ, Kang SY, et al. Paragonimus westermani: molecular cloning, expression, and characterization of a recombinant yolk ferritin. Exp Parasitol 2002;102:194-200

Expert Rev. Anti Infect. Ther.

North American paragonimiasis: epidemiology and diagnostic strategies.

Paragonimiasis is a zoonotic, food-borne trematode infection that affects around 23 million people in Asia, Africa and the Americas. North American pa...
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